Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids     

Deres K  Schröder CH  Paessens A  Goldmann S  Hacker HJ  Weber O  Krämer T  Niewöhner U  Pleiss U  Stoltefuss J  Graef E  Koletzki D  Masantschek RN  Reimann A  Jaeger R  Gross R  Beckermann B  Schlemmer KH  Haebich D  Rübsamen-Waigmann H 《Science (New York, N.Y.)》2003,299(5608):893-896

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe non-nucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection.  相似文献   

Distributions of microbial activities in deep subseafloor sediments   总被引：1，自引：0，他引：1  

D'Hondt S  Jørgensen BB  Miller DJ  Batzke A  Blake R  Cragg BA  Cypionka H  Dickens GR  Ferdelman T  Hinrichs KU  Holm NG  Mitterer R  Spivack A  Wang G  Bekins B  Engelen B  Ford K  Gettemy G  Rutherford SD  Sass H  Skilbeck CG  Aiello IW  Guèrin G  House CH  Inagaki F  Meister P  Naehr T  Niitsuma S  Parkes RJ  Schippers A  Smith DC  Teske A  Wiegel J  Padilla CN  Acosta JL 《Science (New York, N.Y.)》2004,306(5705):2216-2221

Diverse microbial communities and numerous energy-yielding activities occur in deeply buried sediments of the eastern Pacific Ocean. Distributions of metabolic activities often deviate from the standard model. Rates of activities, cell concentrations, and populations of cultured bacteria vary consistently from one subseafloor environment to another. Net rates of major activities principally rely on electron acceptors and electron donors from the photosynthetic surface world. At open-ocean sites, nitrate and oxygen are supplied to the deepest sedimentary communities through the underlying basaltic aquifer. In turn, these sedimentary communities may supply dissolved electron donors and nutrients to the underlying crustal biosphere.  相似文献   

Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase     

Rak A  Pylypenko O  Durek T  Watzke A  Kushnir S  Brunsveld L  Waldmann H  Goody RS  Alexandrov K 《Science (New York, N.Y.)》2003,302(5645):646-650

Rab/Ypt guanosine triphosphatases (GTPases) represent a family of key membrane traffic regulators in eukaryotic cells whose function is governed by the guanosine diphosphate (GDP) dissociation inhibitor (RabGDI). Using a combination of chemical synthesis and protein engineering, we generated and crystallized the monoprenylated Ypt1:RabGDI complex. The structure of the complex was solved to 1.5 angstrom resolution and provides a structural basis for the ability of RabGDI to inhibit the release of nucleotide by Rab proteins. Isoprenoid binding requires a conformational change that opens a cavity in the hydrophobic core of its domain II. Analysis of the structure provides a molecular basis for understanding a RabGDI mutant that causes mental retardation in humans.  相似文献   

Characteristics of misreporters of dietary intake and physical activity     

Rasmussen LB  Matthiessen J  Biltoft-Jensen A  Tetens I 《Public health nutrition》2007,10(3):230-237

OBJECTIVE: To characterise misreporters of energy intake (EI) and energy expenditure (EE). DESIGN: Cross-sectional study, using a validated position and motion instrument, ActiReg, as the reference method to study misreporters of EI and of EE. EI was measured using a dietary record and EE using a physical activity questionnaire (PAQ). Misreporters were defined as subjects outside the 95% confidence limits of agreement between EI or EE reported/EE measured. SETTING: Free-living Danish volunteers. SUBJECTS: One hundred and thirty-eight volunteers aged between 20 and 59 years. RESULTS: Body mass index, smoking, 'try to eat healthily' and worries about weight were related to degree of under-reported EI. The percentage energy from added sugar was lowest (P < 0.001) and the percentage energy from protein (P < 0.001) highest in under-reporters compared with acceptable reporters. Subjects who reported being very physically active at work or in leisure time reported a higher EE than measured EE compared with less physically active subjects (P < 0.05). Likewise, subjects who regard themselves as fit or very fit reported a higher EE than subjects who regard themselves as moderately fit (P < 0.05). Possible over-reporters reported less time as very light activity (P = 0.007), more time as moderate activity (P = 0.01) and more time as vigorous activity (P = 0.02) than acceptable reporters. CONCLUSIONS: Under-reporting of EI should always be taken into consideration; however, only a few characteristics of under-reporters are consistent among studies. Misreporting of EI was more prevalent than misreporting of EE. The level of physical activity more than the time spent involved in various activities was misreported.  相似文献   

Mulching potatoes: Aspects of mulch management systems and soil erosion   总被引：1，自引：0，他引：1  

Linnell M. Edwards  Anja Volk  Jack R. Burney 《American Journal of Potato Research》2000,77(4):225-232

Intensive potato production occupies much of the sloping arable land of Prince Edward Island, Canada, and is at the center of soil erosion concerns in this province. Corrective considerations have turned recent attention to mulching, but there is limited knowledge of its workability or effectiveness in potato systems. This study looks at the effect of mulching on soil loss from potatoes grown on standard erosion plots, and examines a relatively simple approach to assessing soil-surface splash detachment (splash erosion) under mulch-management systems with potatoes. Three sizes of splash cup (25, 50, and 100 mm in diameter) were used under simulated rainfall at 150 mm·h^?1 for 10 minutes to measure splash erosion on potato plots under mulch-management systems which, respectively, left surface coverage of ～ 5%, ～ 15%, and ～20%. The lowest straw coverage gave up to 56% more erosion than either of the two higher coverages. The 25-mm splash cup yielded 14% more sediment splash than the 100-mm splash cup on the basis of unit surface area of soil in the splash cup (unit area). Regression modeling of unit-area splash against straw cover showed an exponential decay in splash detachment with increasing straw cover. On the erosion plots, soil loss with mulching was half of what it was without mulching; and soil water retention was 5% greater with mulching.  相似文献   

Monitoring infection with Piscine myocarditis virus and development of cardiomyopathy syndrome in farmed Atlantic salmon (Salmo salar L.) in Norway     

Julie Christine Svendsen  Stian Nylund  Anja B. Kristoffersen  Harald Takle  Julia Fossberg Buhaug  Britt Bang Jensen 《Journal of fish diseases》2019,42(4):511-518

An epidemiological study was carried out in Norway in 2015–2018, investigating the development of infection with Piscine myocarditis virus (PMCV) and development of cardiomyopathy syndrome (CMS) in farmed Atlantic salmon. Cohorts from 12 sites were followed and sampled every month or every other month from sea transfer to slaughter. PMCV was detected at all sites and in all sampled cages, and fish in six sites developed clinical CMS. The initial infection happened between 1 and 7 months post‐sea transfer, and the median time from infection with PMCV until outbreak of CMS was 6.5 months. Generally, fish from sites with CMS had higher viral titre and a higher prevalence of PMCV, compared to sites that did not develop clinical CMS. The virus persisted until the point of slaughter at most (11 out of 12) of the sites. The detection of PMCV in all sites suggests that PMCV is more widespread than previously known. Screening for PMCV as a tool to monitor impending outbreaks of CMS must be supported by observations of the health status of the fish and risk factors for development of disease.  相似文献   

Lupin kernel meal as fishmeal replacement in formulated feeds for the Whiteleg Shrimp (Litopenaeus vannamei)     

Monika Weiss  Anja Rebelein  Matthew J. Slater 《Aquaculture Nutrition》2020,26(3):752-762

Rapidly expanding global aquaculture requires sustainable, local protein sources to supplement the use of fishmeal. Lupin seed meal (Lupinus angustifolius) was tested as sustainable diet component for Whiteleg shrimp (Litopenaeus vannamei). Controlled feeding experiments were conducted in a recirculating aquaculture system for eight weeks. Juvenile shrimps were provided formulated diets containing various levels of lupin meal inclusion (0, 100, 200 and 300 g kg^?1) supplementing the fishmeal component, and a commercial feed as general reference. Shrimp survival, growth, metabolic and immune parameters were analysed. Survival did not differ significantly between groups. Growth performance was significantly impaired in shrimp fed diets containing more than 100 g kg^?1 lupin meal. Lupin meal supplementation did not affect haemolymph protein content, whereas glucose and acylglyceride concentrations varied between treatments and were highest in animals fed the 100 g kg^?1 lupin meal diet. Phenoloxidase activity was highest in shrimp fed 100 g kg^?1 lupin meal diet indicating improved immune status. The present study indicates that low inclusion levels of lupin meal do not cause adverse effects and seem to stimulate the immune system of juvenile L. vannamei.  相似文献